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X-inactivation patch size in human female tissue confounds the assessment of tumor clonality. (Articolo in rivista)

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X-inactivation patch size in human female tissue confounds the assessment of tumor clonality. (Articolo in rivista) (literal)

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Novelli M, Cossu A, Oukrif D, Quaglia A, Lakhani S, Poulsom R, Sasieni P, Carta P, Contini M, Pasca A, Palmieri G, Bodmer W, Tanda F, Wright N. (2003)
X-inactivation patch size in human female tissue confounds the assessment of tumor clonality.
in Proceedings of the National Academy of Sciences of the United States of America
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Novelli M, Cossu A, Oukrif D, Quaglia A, Lakhani S, Poulsom R, Sasieni P, Carta P, Contini M, Pasca A, Palmieri G, Bodmer W, Tanda F, Wright N. (literal)

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Department of Histopathology, Rockefeller Building, University Street, University College London Hospitals, London WC1E 6JJ, United Kingdom; Azienda USL1, 07100 Sassari, Italy; Department of Histopathology, Royal Free and University College Medical School, Rowland Hill Street, Hampstead, London NW3 2PF, United Kingdom; The Breakthrough Toby Robins Breast Cancer Research, Institute of Cancer Research, Fulham Road, London SW3 6JB, United Kingdom; Cancer Research U.K., P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom; Institute of Pathology, University of Sassari, Via Matteotti 58, 07100 Sassari, Italy; Institute of Molecular Genetics, Consiglio Nazionale delle Ricerche, Localita` Tramariglio, 07040 Santa Maria La Palma (Sassari), Italy; and Cancer and Immunogenetics Laboratory, Cancer Research U.K., Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom (literal)

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X-inactivation patch size in human female tissue confounds the assessment of tumor clonality. (literal)

Abstract

Most models of tumorigenesis assume that tumours are monoclonal in origin. This conclusion is based largely on studies using X-chromosome linked markers in females. One important factor, often ignored in such studies is the distribution of X-inactivated cells in tissues. Since Lyonisation occurs early in development many of the progeny of a single embryonic stem cell are grouped together in the adult forming patches. As polyclonality can only be demonstrated at the borders of X-inactivation patches the patch size is crucial in determining the chance of demonstrating polyclonality and hence the number of tumours that need to be examined to exclude polyclonality. Previously studies using X-linked genes such as glucose-6-phosphate dehydrogenase (G6PD) have been handicapped by the need to destroy the tissues to study the haplotypes of glucose-6-phosphate dehydrogenase1 or to determine the restriction fragment length polymorphisms of X chromosome-linked genes2. Here for the first time we directly visualise X-inactivation patches in human females and show that the patch size in both the human colon and breast is relatively large, confounding assessment of tumour clonality using traditional X-inactivation studies. (literal)

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